Stick or twist? Cost-effectiveness of siponimod compared with continuing existing disease-modifying therapies in the treatment of active secondary progressive multiple sclerosis in the UK

Abstract

Objective

Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated.

Methods

A cohort Markov model based on disease progression through Expanded Disability Status Scale health states, with annual cycles and lifetime horizon, was employed to determine the cost-effectiveness of siponimod from a UK National Health Service (NHS) perspective for patients with active SPMS. Baseline characteristics, health state utility values, hazard ratios for time to 6-month confirmed disability progression, annualized relapse rate ratios and adverse events for siponimod were obtained from the phase 3 EXPAND clinical trial, supplemented by published literature. Published costs, resource use data and comparator efficacy data were obtained from the literature and, in the absence of data, reasonable assumptions were made.

Results

Quality-adjusted life years (QALYs) were greater for siponimod versus all comparators (3.45 versus 2.69–2.83). Incremental cost-effectiveness ratios (ICERs), calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY.

Conclusions

Recognition of active SPMS and treatment of this phenotype with siponimod offers a cost-effective and clinically beneficial treatment approach compared with the continuation of oral or infused RRMS DMTs.

Keywords:

• Secondary progressive multiple sclerosis
• siponimod
• cost-effectiveness
• disease-modifying therapy
• National Health Service

JEL Classification Codes:

• C63
• C6
• C
• I19
• I1
• I

Transparency

Declaration of funding

This research was funded by Novartis Pharmaceuticals UK Ltd.

Declaration of financial/other interests

SM and FW are employees of Costello Medical, who were contracted by Novartis Pharmaceuticals UK Ltd to undertake the work. UV is an employee of Novartis Ireland Limited. KG is an employee of Novartis Healthcare Private Limited. MD has received honoraria for advisory boards, speaker’s fees, research funding and expenses to attend educational events from Novartis, Biogen, Sanofi Genzyme, Teva, Mylan, Roche and TG Therapeutics. MK was an employee of Novartis Pharmaceuticals UK Ltd when this analysis was conducted and is now an employee of Novartis Pharma AG and a Novartis shareholder.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Substantial contributions to study conception and design: SM, FW, UV, KG, MK; substantial contributions to analysis and interpretation of the data: SM, FW, UV, KG, MD, MK; drafting the article or revising it critically for important intellectual content: SM, FW, UV, KG, MD, MK; final approval of the version of the article to be published: SM, FW, UV, KG, MD, MK.

Acknowledgements

The authors would like to acknowledge Nicholas Adlard, Novartis Pharma AG, Basel, Switzerland, for support with model development. Medical writing assistance was provided by Luke Green, Costello Medical, Cambridge, UK.

Previous presentations

An interim analysis and the corresponding results were presented at virtual ISPOR Europe 2021.